Antigen-Specific Adaptive Immunity to SARS-CoV-2 in Acute COVID-19 and Associations with Age and Disease Severity

Carolyn Rydyznski Moderbacher, Sydney I. Ramirez, Jennifer M. Dan, Alba Grifoni, Kathryn M. Hastie, Daniela Weiskopf, Simon Belanger, Robert K. Abbott, Christina Kim, Jinyong Choi, Yu Kato, Eleanor G. Crotty, Cheryl Kim, Stephen A. Rawlings, Jose Mateus, Long Ping Victor Tse, April Frazier, Ralph Baric, Bjoern Peters, Jason GreenbaumErica Ollmann Saphire, Davey M. Smith, Alessandro Sette, Shane Crotty

Research output: Contribution to journalArticlepeer-review


Limited knowledge is available on the relationship between antigen-specific immune responses and COVID-19 disease severity. We completed a combined examination of all three branches of adaptive immunity at the level of SARS-CoV-2-specific CD4+ and CD8+ T cell and neutralizing antibody responses in acute and convalescent subjects. SARS-CoV-2-specific CD4+ and CD8+ T cells were each associated with milder disease. Coordinated SARS-CoV-2-specific adaptive immune responses were associated with milder disease, suggesting roles for both CD4+ and CD8+ T cells in protective immunity in COVID-19. Notably, coordination of SARS-CoV-2 antigen-specific responses was disrupted in individuals ≥ 65 years old. Scarcity of naive T cells was also associated with aging and poor disease outcomes. A parsimonious explanation is that coordinated CD4+ T cell, CD8+ T cell, and antibody responses are protective, but uncoordinated responses frequently fail to control disease, with a connection between aging and impaired adaptive immune responses to SARS-CoV-2.

Original languageEnglish (US)
Pages (from-to)996-1012.e19
Issue number4
StatePublished - Nov 12 2020
Externally publishedYes


  • CD4
  • CD8
  • CXCL10
  • IP-10
  • Spike
  • T cells
  • adaptive immunity
  • antibody
  • coronavirus
  • epitopes
  • neutralizing antibodies

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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